MAPK2_HUMAN
ID MAPK2_HUMAN Reviewed; 400 AA.
AC P49137; Q5SY30; Q5SY41; Q8IYD6;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 216.
DE RecName: Full=MAP kinase-activated protein kinase 2;
DE Short=MAPK-activated protein kinase 2;
DE Short=MAPKAP kinase 2;
DE Short=MAPKAP-K2;
DE Short=MAPKAPK-2;
DE Short=MK-2;
DE Short=MK2;
DE EC=2.7.11.1;
GN Name=MAPKAPK2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=8179591; DOI=10.1006/bbrc.1994.1566;
RA Zu Y.-L., Wu F., Gilchrist A., Ai Y., Labadia M.E., Huang C.K.;
RT "The primary structure of a human MAP kinase activated protein kinase 2.";
RL Biochem. Biophys. Res. Commun. 200:1118-1124(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skin, and Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 5-400 (ISOFORM 1), AND FUNCTION.
RX PubMed=8280084; DOI=10.1042/bj2960843;
RA Stokoe D., Caudwell B., Cohen P.T.W., Cohen P.;
RT "The substrate specificity and structure of mitogen-activated protein (MAP)
RT kinase-activated protein kinase-2.";
RL Biochem. J. 296:843-849(1993).
RN [6]
RP FUNCTION IN PHOSPHORYLATION OF HSPB1.
RX PubMed=8093612; DOI=10.1016/s0021-9258(18)53882-5;
RA Jakob U., Gaestel M., Engel K., Buchner J.;
RT "Small heat shock proteins are molecular chaperones.";
RL J. Biol. Chem. 268:1517-1520(1993).
RN [7]
RP PHOSPHORYLATION AT SER-9; THR-25; THR-222; SER-272 AND THR-334, AND
RP MUTAGENESIS OF ASP-207; THR-222; SER-272 AND THR-334.
RX PubMed=8846784; DOI=10.1002/j.1460-2075.1995.tb00280.x;
RA Ben-Levy R., Leighton I.A., Doza Y.N., Attwood P., Morrice N.,
RA Marshall C.J., Cohen P.;
RT "Identification of novel phosphorylation sites required for activation of
RT MAPKAP kinase-2.";
RL EMBO J. 14:5920-5930(1995).
RN [8]
RP CATALYTIC ACTIVITY, AND FUNCTION IN PHOSPHORYLATION OF HSPB1.
RX PubMed=8774846; DOI=10.1016/0014-5793(96)00816-2;
RA Clifton A.D., Young P.R., Cohen P.;
RT "A comparison of the substrate specificity of MAPKAP kinase-2 and MAPKAP
RT kinase-3 and their activation by cytokines and cellular stress.";
RL FEBS Lett. 392:209-214(1996).
RN [9]
RP FUNCTION IN PHOSPHORYLATION OF HSPB1.
RX PubMed=10383393; DOI=10.1074/jbc.274.27.18947;
RA Rogalla T., Ehrnsperger M., Preville X., Kotlyarov A., Lutsch G.,
RA Ducasse C., Paul C., Wieske M., Arrigo A.P., Buchner J., Gaestel M.;
RT "Regulation of Hsp27 oligomerization, chaperone function, and protective
RT activity against oxidative stress/tumor necrosis factor alpha by
RT phosphorylation.";
RL J. Biol. Chem. 274:18947-18956(1999).
RN [10]
RP FUNCTION IN PHOSPHORYLATION OF HNRNPA0.
RX PubMed=12456657; DOI=10.1093/emboj/cdf639;
RA Rousseau S., Morrice N., Peggie M., Campbell D.G., Gaestel M., Cohen P.;
RT "Inhibition of SAPK2a/p38 prevents hnRNP A0 phosphorylation by MAPKAP-K2
RT and its interaction with cytokine mRNAs.";
RL EMBO J. 21:6505-6514(2002).
RN [11]
RP FUNCTION IN PHOSPHORYLATION OF LOX5.
RX PubMed=11844797; DOI=10.1074/jbc.m111945200;
RA Werz O., Szellas D., Steinhilber D., Radmark O.;
RT "Arachidonic acid promotes phosphorylation of 5-lipoxygenase at Ser-271 by
RT MAPK-activated protein kinase 2 (MK2).";
RL J. Biol. Chem. 277:14793-14800(2002).
RN [12]
RP FUNCTION IN PHOSPHORYLATION OF PABPC1.
RX PubMed=12565831; DOI=10.1016/s0006-291x(03)00015-9;
RA Bollig F., Winzen R., Gaestel M., Kostka S., Resch K., Holtmann H.;
RT "Affinity purification of ARE-binding proteins identifies polyA-binding
RT protein 1 as a potential substrate in MK2-induced mRNA stabilization.";
RL Biochem. Biophys. Res. Commun. 301:665-670(2003).
RN [13]
RP FUNCTION.
RX PubMed=14499342; DOI=10.1016/s0898-6568(03)00074-3;
RA Coxon P.Y., Rane M.J., Uriarte S., Powell D.W., Singh S., Butt W., Chen Q.,
RA McLeish K.R.;
RT "MAPK-activated protein kinase-2 participates in p38 MAPK-dependent and
RT ERK-dependent functions in human neutrophils.";
RL Cell. Signal. 15:993-1001(2003).
RN [14]
RP FUNCTION IN PHOSPHORYLATION OF ELAVL1, AND MUTAGENESIS OF LYS-93; THR-222
RP AND THR-334.
RX PubMed=14517288; DOI=10.1128/mcb.23.20.7177-7188.2003;
RA Tran H., Maurer F., Nagamine Y.;
RT "Stabilization of urokinase and urokinase receptor mRNAs by HuR is linked
RT to its cytoplasmic accumulation induced by activated mitogen-activated
RT protein kinase-activated protein kinase 2.";
RL Mol. Cell. Biol. 23:7177-7188(2003).
RN [15]
RP FUNCTION IN PHOSPHORYLATION OF ZFP36, AND MUTAGENESIS OF THR-222 AND
RP THR-334.
RX PubMed=15014438; DOI=10.1038/sj.emboj.7600163;
RA Stoecklin G., Stubbs T., Kedersha N., Wax S., Rigby W.F., Blackwell T.K.,
RA Anderson P.;
RT "MK2-induced tristetraprolin:14-3-3 complexes prevent stress granule
RT association and ARE-mRNA decay.";
RL EMBO J. 23:1313-1324(2004).
RN [16]
RP INTERACTION WITH PHC2.
RX PubMed=15094067; DOI=10.1016/s0014-5793(04)00351-5;
RA Yannoni Y.M., Gaestel M., Lin L.L.;
RT "P66(ShcA) interacts with MAPKAP kinase 2 and regulates its activity.";
RL FEBS Lett. 564:205-211(2004).
RN [17]
RP FUNCTION IN PHOSPHORYLATION OF CDC25B AND CDC25C.
RX PubMed=15629715; DOI=10.1016/j.molcel.2004.11.021;
RA Manke I.A., Nguyen A., Lim D., Stewart M.Q., Elia A.E., Yaffe M.B.;
RT "MAPKAP kinase-2 is a cell cycle checkpoint kinase that regulates the G2/M
RT transition and S phase progression in response to UV irradiation.";
RL Mol. Cell 17:37-48(2005).
RN [18]
RP FUNCTION IN PHOSPHORYLATION OF LIMK1.
RX PubMed=16456544; DOI=10.1038/sj.emboj.7600973;
RA Kobayashi M., Nishita M., Mishima T., Ohashi K., Mizuno K.;
RT "MAPKAPK-2-mediated LIM-kinase activation is critical for VEGF-induced
RT actin remodeling and cell migration.";
RL EMBO J. 25:713-726(2006).
RN [19]
RP FUNCTION IN PHOSPHORYLATION OF HSF1, AND INTERACTION WITH HSF1.
RX PubMed=16278218; DOI=10.1074/jbc.m505822200;
RA Wang X., Khaleque M.A., Zhao M.J., Zhong R., Gaestel M., Calderwood S.K.;
RT "Phosphorylation of HSF1 by MAPK-activated protein kinase 2 on serine 121,
RT inhibits transcriptional activity and promotes HSP90 binding.";
RL J. Biol. Chem. 281:782-791(2006).
RN [20]
RP FUNCTION IN PHOSPHORYLATION OF LSP1.
RX PubMed=17481585; DOI=10.1016/j.bbrc.2007.04.104;
RA Wu Y., Zhan L., Ai Y., Hannigan M., Gaestel M., Huang C.-K., Madri J.A.;
RT "MAPKAPK2-mediated LSP1 phosphorylation and FMLP-induced neutrophil
RT polarization.";
RL Biochem. Biophys. Res. Commun. 358:170-175(2007).
RN [21]
RP FUNCTION IN PHOSPHORYLATION OF TAB3.
RX PubMed=18021073; DOI=10.1042/bj20071149;
RA Mendoza H., Campbell D.G., Burness K., Hastie J., Ronkina N., Shim J.H.,
RA Arthur J.S., Davis R.J., Gaestel M., Johnson G.L., Ghosh S., Cohen P.;
RT "Roles for TAB1 in regulating the IL-1-dependent phosphorylation of the
RT TAB3 regulatory subunit and activity of the TAK1 complex.";
RL Biochem. J. 409:711-722(2008).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [23]
RP FUNCTION IN PHOSPHORYLATION OF HNRNPA0 AND PARN, AND SUBCELLULAR LOCATION.
RX PubMed=20932473; DOI=10.1016/j.molcel.2010.09.018;
RA Reinhardt H.C., Hasskamp P., Schmedding I., Morandell S., van Vugt M.A.,
RA Wang X., Linding R., Ong S.E., Weaver D., Carr S.A., Yaffe M.B.;
RT "DNA damage activates a spatially distinct late cytoplasmic cell-cycle
RT checkpoint network controlled by MK2-mediated RNA stabilization.";
RL Mol. Cell 40:34-49(2010).
RN [24]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [25]
RP SUMOYLATION AT LYS-353, AND MUTAGENESIS OF LYS-353.
RX PubMed=21131586; DOI=10.1182/blood-2010-08-302281;
RA Chang E., Heo K.S., Woo C.H., Lee H., Le N.T., Thomas T.N., Fujiwara K.,
RA Abe J.;
RT "MK2 SUMOylation regulates actin filament remodeling and subsequent
RT migration in endothelial cells by inhibiting MK2 kinase and HSP27
RT phosphorylation.";
RL Blood 117:2527-2537(2011).
RN [26]
RP REVIEW.
RX PubMed=18508601; DOI=10.2741/3095;
RA Ronkina N., Kotlyarov A., Gaestel M.;
RT "MK2 and MK3--a pair of isoenzymes?";
RL Front. Biosci. 13:5511-5521(2008).
RN [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-334, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-334, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [29]
RP FUNCTION.
RX PubMed=26616734; DOI=10.1038/ncomms10075;
RA Tollenaere M.A., Villumsen B.H., Blasius M., Nielsen J.C., Wagner S.A.,
RA Bartek J., Beli P., Mailand N., Bekker-Jensen S.;
RT "p38- and MK2-dependent signalling promotes stress-induced centriolar
RT satellite remodelling via 14-3-3-dependent sequestration of CEP131/AZI1.";
RL Nat. Commun. 6:10075-10075(2015).
RN [30]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) IN COMPLEX WITH ADP AND
RP STAUROSPORINE, AND CATALYTIC ACTIVITY.
RX PubMed=12171911; DOI=10.1074/jbc.c200418200;
RA Meng W., Swenson L.L., Fitzgibbon M.J., Hayakawa K., Ter Haar E.,
RA Behrens A.E., Fulghum J.R., Lippke J.A.;
RT "Structure of mitogen-activated protein kinase-activated protein (MAPKAP)
RT kinase 2 suggests a bifunctional switch that couples kinase activation with
RT nuclear export.";
RL J. Biol. Chem. 277:37401-37405(2002).
RN [31]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS).
RX PubMed=12791252; DOI=10.1016/s0969-2126(03)00092-3;
RA Underwood K.W., Parris K.D., Federico E., Mosyak L., Czerwinski R.M.,
RA Shane T., Taylor M., Svenson K., Liu Y., Hsiao C.L., Wolfrom S.,
RA Maguire M., Malakian K., Telliez J.B., Lin L.L., Kriz R.W., Seehra J.,
RA Somers W.S., Stahl M.L.;
RT "Catalytically active MAP KAP kinase 2 structures in complex with
RT staurosporine and ADP reveal differences with the autoinhibited enzyme.";
RL Structure 11:627-636(2003).
RN [32]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 41-364 IN COMPLEX WITH
RP CARBOLINE-BASED INHIBITORS.
RX PubMed=17576063; DOI=10.1016/j.bmcl.2007.05.101;
RA Wu J.P., Wang J., Abeywardane A., Andersen D., Emmanuel M., Gautschi E.,
RA Goldberg D.R., Kashem M.A., Lukas S., Mao W., Martin L., Morwick T.,
RA Moss N., Pargellis C., Patel U.R., Patnaude L., Peet G.W., Skow D.,
RA Snow R.J., Ward Y., Werneburg B., White A.;
RT "The discovery of carboline analogs as potent MAPKAP-K2 inhibitors.";
RL Bioorg. Med. Chem. Lett. 17:4664-4669(2007).
RN [33]
RP X-RAY CRYSTALLOGRAPHY (4.0 ANGSTROMS) IN COMPLEX WITH MAPK14, AND
RP INTERACTION WITH MAPK14.
RX PubMed=17255097; DOI=10.1074/jbc.m611165200;
RA ter Haar E., Prabhakar P., Liu X., Lepre C.;
RT "Crystal structure of the p38 alpha-MAPKAP kinase 2 heterodimer.";
RL J. Biol. Chem. 282:9733-9739(2007).
RN [34]
RP ERRATUM OF PUBMED:17255097.
RA ter Haar E., Prabhakar P., Liu X., Lepre C.;
RL J. Biol. Chem. 282:14684-14684(2007).
RN [35]
RP X-RAY CRYSTALLOGRAPHY (3.8 ANGSTROMS) OF 45-371 IN COMPLEX WITH
RP PYRROLOPYRIDINE INHIBITORS.
RX PubMed=17480064; DOI=10.1021/jm0611004;
RA Anderson D.R., Meyers M.J., Vernier W.F., Mahoney M.W., Kurumbail R.G.,
RA Caspers N., Poda G.I., Schindler J.F., Reitz D.B., Mourey R.J.;
RT "Pyrrolopyridine inhibitors of mitogen-activated protein kinase-activated
RT protein kinase 2 (MK-2).";
RL J. Med. Chem. 50:2647-2654(2007).
RN [36]
RP X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 41-364 IN COMPLEX WITH
RP PYRROLOPYRIDINE INHIBITOR.
RX PubMed=17449059; DOI=10.1016/j.jmb.2007.03.004;
RA Hillig R.C., Eberspaecher U., Monteclaro F., Huber M., Nguyen D.,
RA Mengel A., Muller-Tiemann B., Egner U.;
RT "Structural basis for a high affinity inhibitor bound to protein kinase
RT MK2.";
RL J. Mol. Biol. 369:735-745(2007).
RN [37]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 47-400 IN COMPLEX WITH MAPK14, AND
RP INTERACTION WITH MAPK14.
RX PubMed=17395714; DOI=10.1073/pnas.0701679104;
RA White A., Pargellis C.A., Studts J.M., Werneburg B.G., Farmer B.T. II;
RT "Molecular basis of MAPK-activated protein kinase 2:p38 assembly.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:6353-6358(2007).
RN [38]
RP VARIANTS [LARGE SCALE ANALYSIS] GLY-173 AND SER-361.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Stress-activated serine/threonine-protein kinase involved in
CC cytokine production, endocytosis, reorganization of the cytoskeleton,
CC cell migration, cell cycle control, chromatin remodeling, DNA damage
CC response and transcriptional regulation. Following stress, it is
CC phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to
CC phosphorylation of substrates. Phosphorylates serine in the peptide
CC sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue.
CC Phosphorylates ALOX5, CDC25B, CDC25C, CEP131, ELAVL1, HNRNPA0,
CC HSP27/HSPB1, KRT18, KRT20, LIMK1, LSP1, PABPC1, PARN, PDE4A, RCSD1,
CC RPS6KA3, TAB3 and TTP/ZFP36. Phosphorylates HSF1; leading to the
CC interaction with HSP90 proteins and inhibiting HSF1 homotrimerization,
CC DNA-binding and transactivation activities (PubMed:16278218). Mediates
CC phosphorylation of HSP27/HSPB1 in response to stress, leading to the
CC dissociation of HSP27/HSPB1 from large small heat-shock protein (sHsps)
CC oligomers and impairment of their chaperone activities and ability to
CC protect against oxidative stress effectively. Involved in inflammatory
CC response by regulating tumor necrosis factor (TNF) and IL6 production
CC post-transcriptionally: acts by phosphorylating AU-rich elements
CC (AREs)-binding proteins ELAVL1, HNRNPA0, PABPC1 and TTP/ZFP36, leading
CC to the regulation of the stability and translation of TNF and IL6
CC mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional
CC regulator of TNF, promotes its binding to 14-3-3 proteins and reduces
CC its ARE mRNA affinity, leading to inhibition of dependent degradation
CC of ARE-containing transcripts. Phosphorylates CEP131 in response to
CC cellular stress induced by ultraviolet irradiation which promotes
CC binding of CEP131 to 14-3-3 proteins and inhibits formation of novel
CC centriolar satellites (PubMed:26616734). Also involved in late G2/M
CC checkpoint following DNA damage through a process of post-
CC transcriptional mRNA stabilization: following DNA damage, relocalizes
CC from nucleus to cytoplasm and phosphorylates HNRNPA0 and PARN, leading
CC to stabilization of GADD45A mRNA. Involved in toll-like receptor
CC signaling pathway (TLR) in dendritic cells: required for acute TLR-
CC induced macropinocytosis by phosphorylating and activating RPS6KA3.
CC {ECO:0000269|PubMed:10383393, ECO:0000269|PubMed:11844797,
CC ECO:0000269|PubMed:12456657, ECO:0000269|PubMed:12565831,
CC ECO:0000269|PubMed:14499342, ECO:0000269|PubMed:14517288,
CC ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:15629715,
CC ECO:0000269|PubMed:16278218, ECO:0000269|PubMed:16456544,
CC ECO:0000269|PubMed:17481585, ECO:0000269|PubMed:18021073,
CC ECO:0000269|PubMed:20932473, ECO:0000269|PubMed:26616734,
CC ECO:0000269|PubMed:8093612, ECO:0000269|PubMed:8280084,
CC ECO:0000269|PubMed:8774846}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000269|PubMed:12171911, ECO:0000269|PubMed:8774846};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000269|PubMed:12171911,
CC ECO:0000269|PubMed:8774846};
CC -!- ACTIVITY REGULATION: Activated following phosphorylation by p38-
CC alpha/MAPK14 following various stresses. Inhibited following
CC sumoylation. Specifically inhibited by pyrrolopyridine inhibitors.
CC -!- SUBUNIT: Heterodimer with p38-alpha/MAPK14; this heterodimer forms a
CC stable complex: molecules are positioned 'face to face' so that the
CC ATP-binding sites of both kinases are at the heterodimer interface
CC (PubMed:12171911, PubMed:17576063, PubMed:17255097, PubMed:17480064,
CC PubMed:17449059, PubMed:17395714). Interacts with PHC2
CC (PubMed:15094067). Interacts with HSF1 (PubMed:16278218).
CC {ECO:0000269|PubMed:12171911, ECO:0000269|PubMed:15094067,
CC ECO:0000269|PubMed:16278218, ECO:0000269|PubMed:17255097,
CC ECO:0000269|PubMed:17395714, ECO:0000269|PubMed:17449059,
CC ECO:0000269|PubMed:17480064, ECO:0000269|PubMed:17576063}.
CC -!- INTERACTION:
CC P49137; Q00613: HSF1; NbExp=5; IntAct=EBI-993299, EBI-719620;
CC P49137; P04792: HSPB1; NbExp=3; IntAct=EBI-993299, EBI-352682;
CC P49137; Q16539: MAPK14; NbExp=10; IntAct=EBI-993299, EBI-73946;
CC P49137; Q9QWH1: Phc2; Xeno; NbExp=2; IntAct=EBI-993299, EBI-642357;
CC P49137-1; P47811: Mapk14; Xeno; NbExp=2; IntAct=EBI-15629963, EBI-298727;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:20932473}. Nucleus
CC {ECO:0000269|PubMed:20932473}. Note=Phosphorylation and subsequent
CC activation releases the autoinhibitory helix, resulting in the export
CC from the nucleus into the cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P49137-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P49137-2; Sequence=VSP_004910;
CC -!- TISSUE SPECIFICITY: Expressed in all tissues examined.
CC -!- PTM: Sumoylation inhibits the protein kinase activity.
CC {ECO:0000269|PubMed:21131586}.
CC -!- PTM: Phosphorylated and activated by MAP kinase p38-alpha/MAPK14 at
CC Thr-222, Ser-272 and Thr-334. {ECO:0000269|PubMed:8846784}.
CC -!- MISCELLANEOUS: [Isoform 1]: Has a nuclear localization signal.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/MAPKAPK2ID41295ch1q32.html";
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DR EMBL; U12779; AAA20851.1; -; mRNA.
DR EMBL; AL591846; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471100; EAW93526.1; -; Genomic_DNA.
DR EMBL; CH471100; EAW93529.1; -; Genomic_DNA.
DR EMBL; BC036060; AAH36060.2; -; mRNA.
DR EMBL; BC052584; AAH52584.1; -; mRNA.
DR EMBL; X75346; CAA53094.1; -; mRNA.
DR CCDS; CCDS1466.1; -. [P49137-2]
DR CCDS; CCDS31001.1; -. [P49137-1]
DR PIR; JC2204; JC2204.
DR PIR; S39793; S39793.
DR RefSeq; NP_004750.1; NM_004759.4. [P49137-2]
DR RefSeq; NP_116584.2; NM_032960.3. [P49137-1]
DR PDB; 1KWP; X-ray; 2.80 A; A/B=1-400.
DR PDB; 1NXK; X-ray; 2.70 A; A/B/C/D=1-400.
DR PDB; 1NY3; X-ray; 3.00 A; A=1-400.
DR PDB; 2JBO; X-ray; 3.10 A; A=41-364.
DR PDB; 2JBP; X-ray; 3.31 A; A/B/C/D/E/F/G/H/I/J/K/L=41-364.
DR PDB; 2OKR; X-ray; 2.00 A; C/F=370-393.
DR PDB; 2ONL; X-ray; 4.00 A; C/D=1-400.
DR PDB; 2OZA; X-ray; 2.70 A; A=47-400.
DR PDB; 2P3G; X-ray; 3.80 A; X=45-371.
DR PDB; 2PZY; X-ray; 2.90 A; A/B/C/D=41-364.
DR PDB; 3A2C; X-ray; 2.90 A; A/B/C/D/E/F/G/H/I/J/K/L=41-364.
DR PDB; 3FPM; X-ray; 3.30 A; A=41-364.
DR PDB; 3FYJ; X-ray; 3.80 A; X=45-371.
DR PDB; 3FYK; X-ray; 3.50 A; X=45-371.
DR PDB; 3GOK; X-ray; 3.20 A; A/B/C/D/E/F/G/H/I/J/K/L=41-364.
DR PDB; 3KA0; X-ray; 2.90 A; A=47-366.
DR PDB; 3KC3; X-ray; 2.90 A; A/B/C/D/E/F/G/H/I/J/K/L=41-364.
DR PDB; 3KGA; X-ray; 2.55 A; A=47-364.
DR PDB; 3M2W; X-ray; 2.41 A; A=47-364.
DR PDB; 3M42; X-ray; 2.68 A; A=47-364.
DR PDB; 3R2B; X-ray; 2.90 A; A/B/C/D/E/F/G/H/I/J/K/L=47-364.
DR PDB; 3R2Y; X-ray; 3.00 A; A=46-364.
DR PDB; 3R30; X-ray; 3.20 A; A=46-364.
DR PDB; 3WI6; X-ray; 2.99 A; A/B/C/D/E/F=41-364.
DR PDB; 4TYH; X-ray; 3.00 A; A=51-400.
DR PDB; 6T8X; X-ray; 2.81 A; A/B/C/D/E/F=41-338.
DR PDB; 6TCA; X-ray; 3.70 A; A/C/E/G=41-400.
DR PDB; 7NRY; X-ray; 3.80 A; X=45-371.
DR PDBsum; 1KWP; -.
DR PDBsum; 1NXK; -.
DR PDBsum; 1NY3; -.
DR PDBsum; 2JBO; -.
DR PDBsum; 2JBP; -.
DR PDBsum; 2OKR; -.
DR PDBsum; 2ONL; -.
DR PDBsum; 2OZA; -.
DR PDBsum; 2P3G; -.
DR PDBsum; 2PZY; -.
DR PDBsum; 3A2C; -.
DR PDBsum; 3FPM; -.
DR PDBsum; 3FYJ; -.
DR PDBsum; 3FYK; -.
DR PDBsum; 3GOK; -.
DR PDBsum; 3KA0; -.
DR PDBsum; 3KC3; -.
DR PDBsum; 3KGA; -.
DR PDBsum; 3M2W; -.
DR PDBsum; 3M42; -.
DR PDBsum; 3R2B; -.
DR PDBsum; 3R2Y; -.
DR PDBsum; 3R30; -.
DR PDBsum; 3WI6; -.
DR PDBsum; 4TYH; -.
DR PDBsum; 6T8X; -.
DR PDBsum; 6TCA; -.
DR PDBsum; 7NRY; -.
DR AlphaFoldDB; P49137; -.
DR BMRB; P49137; -.
DR SMR; P49137; -.
DR BioGRID; 114683; 119.
DR DIP; DIP-35671N; -.
DR ELM; P49137; -.
DR IntAct; P49137; 24.
DR MINT; P49137; -.
DR STRING; 9606.ENSP00000356070; -.
DR BindingDB; P49137; -.
DR ChEMBL; CHEMBL2208; -.
DR DrugBank; DB07430; (10R)-10-methyl-3-(6-methylpyridin-3-yl)-9,10,11,12-tetrahydro-8H-[1,4]diazepino[5',6':4,5]thieno[3,2-f]quinolin-8-one.
DR DrugBank; DB07431; (3R)-3-(aminomethyl)-9-methoxy-1,2,3,4-tetrahydro-5H-[1]benzothieno[3,2-e][1,4]diazepin-5-one.
DR DrugBank; DB07406; (4R)-N-[4-({[2-(DIMETHYLAMINO)ETHYL]AMINO}CARBONYL)-1,3-THIAZOL-2-YL]-4-METHYL-1-OXO-2,3,4,9-TETRAHYDRO-1H-BETA-CARBOLINE-6-CARBOXAMIDE.
DR DrugBank; DB08358; 2-(2-QUINOLIN-3-YLPYRIDIN-4-YL)-1,5,6,7-TETRAHYDRO-4H-PYRROLO[3,2-C]PYRIDIN-4-ONE.
DR DrugBank; DB07728; 2-[2-(2-FLUOROPHENYL)PYRIDIN-4-YL]-1,5,6,7-TETRAHYDRO-4H-PYRROLO[3,2-C]PYRIDIN-4-ONE.
DR DrugBank; DB07234; 3-{[(1R)-1-phenylethyl]amino}-4-(pyridin-4-ylamino)cyclobut-3-ene-1,2-dione.
DR DrugBank; DB02010; Staurosporine.
DR DrugCentral; P49137; -.
DR GuidetoPHARMACOLOGY; 2094; -.
DR iPTMnet; P49137; -.
DR PhosphoSitePlus; P49137; -.
DR SwissPalm; P49137; -.
DR BioMuta; MAPKAPK2; -.
DR DMDM; 1346538; -.
DR EPD; P49137; -.
DR jPOST; P49137; -.
DR MassIVE; P49137; -.
DR MaxQB; P49137; -.
DR PaxDb; P49137; -.
DR PeptideAtlas; P49137; -.
DR PRIDE; P49137; -.
DR ProteomicsDB; 55964; -. [P49137-1]
DR ProteomicsDB; 55965; -. [P49137-2]
DR Antibodypedia; 4144; 963 antibodies from 47 providers.
DR DNASU; 9261; -.
DR Ensembl; ENST00000294981.8; ENSP00000294981.4; ENSG00000162889.11. [P49137-2]
DR Ensembl; ENST00000367103.4; ENSP00000356070.4; ENSG00000162889.11. [P49137-1]
DR GeneID; 9261; -.
DR KEGG; hsa:9261; -.
DR MANE-Select; ENST00000367103.4; ENSP00000356070.4; NM_032960.4; NP_116584.2.
DR UCSC; uc001hel.3; human. [P49137-1]
DR CTD; 9261; -.
DR DisGeNET; 9261; -.
DR GeneCards; MAPKAPK2; -.
DR HGNC; HGNC:6887; MAPKAPK2.
DR HPA; ENSG00000162889; Low tissue specificity.
DR MIM; 602006; gene.
DR neXtProt; NX_P49137; -.
DR OpenTargets; ENSG00000162889; -.
DR PharmGKB; PA30631; -.
DR VEuPathDB; HostDB:ENSG00000162889; -.
DR eggNOG; KOG0604; Eukaryota.
DR GeneTree; ENSGT00940000157261; -.
DR HOGENOM; CLU_000288_63_0_1; -.
DR InParanoid; P49137; -.
DR OMA; ARNCENI; -.
DR OrthoDB; 843707at2759; -.
DR PhylomeDB; P49137; -.
DR TreeFam; TF312891; -.
DR BioCyc; MetaCyc:HS08751-MON; -.
DR BRENDA; 2.7.11.1; 2681.
DR PathwayCommons; P49137; -.
DR Reactome; R-HSA-171007; p38MAPK events.
DR Reactome; R-HSA-199920; CREB phosphorylation.
DR Reactome; R-HSA-2142691; Synthesis of Leukotrienes (LT) and Eoxins (EX).
DR Reactome; R-HSA-2559580; Oxidative Stress Induced Senescence.
DR Reactome; R-HSA-3371453; Regulation of HSF1-mediated heat shock response.
DR Reactome; R-HSA-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-HSA-450302; activated TAK1 mediates p38 MAPK activation.
DR Reactome; R-HSA-450385; Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA.
DR Reactome; R-HSA-450513; Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA.
DR SignaLink; P49137; -.
DR SIGNOR; P49137; -.
DR BioGRID-ORCS; 9261; 16 hits in 1116 CRISPR screens.
DR ChiTaRS; MAPKAPK2; human.
DR EvolutionaryTrace; P49137; -.
DR GeneWiki; MAPKAPK2; -.
DR GenomeRNAi; 9261; -.
DR Pharos; P49137; Tchem.
DR PRO; PR:P49137; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P49137; protein.
DR Bgee; ENSG00000162889; Expressed in apex of heart and 200 other tissues.
DR Genevisible; P49137; HS.
DR GO; GO:0005813; C:centrosome; IDA:HPA.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0009931; F:calcium-dependent protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0005516; F:calmodulin binding; IBA:GO_Central.
DR GO; GO:0004683; F:calmodulin-dependent protein kinase activity; IBA:GO_Central.
DR GO; GO:0051019; F:mitogen-activated protein kinase binding; IBA:GO_Central.
DR GO; GO:0004672; F:protein kinase activity; TAS:ProtInc.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0070935; P:3'-UTR-mediated mRNA stabilization; IDA:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IMP:UniProtKB.
DR GO; GO:0035924; P:cellular response to vascular endothelial growth factor stimulus; IMP:BHF-UCL.
DR GO; GO:0006954; P:inflammatory response; ISS:UniProtKB.
DR GO; GO:0048839; P:inner ear development; IEA:Ensembl.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0006691; P:leukotriene metabolic process; TAS:Reactome.
DR GO; GO:0044351; P:macropinocytosis; ISS:UniProtKB.
DR GO; GO:0000165; P:MAPK cascade; TAS:ProtInc.
DR GO; GO:0038066; P:p38MAPK cascade; IEA:Ensembl.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:BHF-UCL.
DR GO; GO:0060907; P:positive regulation of macrophage cytokine production; IEA:Ensembl.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IEA:Ensembl.
DR GO; GO:0046777; P:protein autophosphorylation; IBA:GO_Central.
DR GO; GO:0006468; P:protein phosphorylation; TAS:ProtInc.
DR GO; GO:1900034; P:regulation of cellular response to heat; TAS:Reactome.
DR GO; GO:0032675; P:regulation of interleukin-6 production; ISS:UniProtKB.
DR GO; GO:0043488; P:regulation of mRNA stability; TAS:Reactome.
DR GO; GO:0032680; P:regulation of tumor necrosis factor production; IDA:UniProtKB.
DR GO; GO:0034097; P:response to cytokine; IDA:UniProtKB.
DR GO; GO:0032496; P:response to lipopolysaccharide; ISS:UniProtKB.
DR GO; GO:0002224; P:toll-like receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; IMP:BHF-UCL.
DR Gene3D; 4.10.1170.10; -; 1.
DR IDEAL; IID00271; -.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR027442; MAPKAPK_C.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Cytoplasm; DNA damage;
KW Isopeptide bond; Kinase; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase;
KW Ubl conjugation.
FT CHAIN 1..400
FT /note="MAP kinase-activated protein kinase 2"
FT /id="PRO_0000086288"
FT DOMAIN 64..325
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..43
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 328..364
FT /note="Autoinhibitory helix"
FT /evidence="ECO:0000250"
FT REGION 366..390
FT /note="p38 MAPK-binding site"
FT MOTIF 356..365
FT /note="Nuclear export signal (NES)"
FT MOTIF 371..374
FT /note="Bipartite nuclear localization signal 1"
FT MOTIF 385..389
FT /note="Bipartite nuclear localization signal 2"
FT COMPBIAS 10..43
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 186
FT /note="Proton acceptor"
FT BINDING 70..78
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 93
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 139..141
FT /ligand="staurosporine"
FT /ligand_id="ChEBI:CHEBI:57491"
FT MOD_RES 9
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:8846784"
FT MOD_RES 25
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:8846784"
FT MOD_RES 222
FT /note="Phosphothreonine; by MAPK14"
FT /evidence="ECO:0000269|PubMed:8846784"
FT MOD_RES 272
FT /note="Phosphoserine; by MAPK14"
FT /evidence="ECO:0000269|PubMed:8846784"
FT MOD_RES 328
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 334
FT /note="Phosphothreonine; by MAPK14"
FT /evidence="ECO:0000269|PubMed:8846784,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT CROSSLNK 353
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000269|PubMed:21131586"
FT VAR_SEQ 354..400
FT /note="EEMTSALATMRVDYEQIKIKKIEDASNPLLLKRRKKARALEAAALAH -> G
FT CLHDKNSDQATWLTRL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8179591"
FT /id="VSP_004910"
FT VARIANT 173
FT /note="A -> G (in dbSNP:rs35671930)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040753"
FT VARIANT 361
FT /note="A -> S (in dbSNP:rs55894011)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040754"
FT MUTAGEN 93
FT /note="K->R: Kinase defective mutant, abolishes activity."
FT /evidence="ECO:0000269|PubMed:14517288"
FT MUTAGEN 207
FT /note="D->A: Kinase defective mutant, abolishes activity."
FT /evidence="ECO:0000269|PubMed:8846784"
FT MUTAGEN 222
FT /note="T->A: Strong decrease in kinase activity."
FT /evidence="ECO:0000269|PubMed:14517288,
FT ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:8846784"
FT MUTAGEN 222
FT /note="T->D: Mimicks phosphorylation state, leading to
FT slight increase of basal kinase activity."
FT /evidence="ECO:0000269|PubMed:14517288,
FT ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:8846784"
FT MUTAGEN 222
FT /note="T->E: Mimicks phosphorylation state and constitutive
FT protein kinase activity; when associated with E-334."
FT /evidence="ECO:0000269|PubMed:14517288,
FT ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:8846784"
FT MUTAGEN 272
FT /note="S->A: Strong decrease in kinase activity."
FT /evidence="ECO:0000269|PubMed:8846784"
FT MUTAGEN 272
FT /note="S->D: Mimicks phosphorylation state, leading to
FT slight increase of basal kinase activity."
FT /evidence="ECO:0000269|PubMed:8846784"
FT MUTAGEN 334
FT /note="T->A: Slight decrease in kinase activity."
FT /evidence="ECO:0000269|PubMed:14517288,
FT ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:8846784"
FT MUTAGEN 334
FT /note="T->D,E: Mimicks phosphorylation state, leading to
FT elevated basal kinase activity."
FT /evidence="ECO:0000269|PubMed:14517288,
FT ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:8846784"
FT MUTAGEN 334
FT /note="T->E: Mimicks phosphorylation state and constitutive
FT protein kinase activity; when associated with E-222."
FT /evidence="ECO:0000269|PubMed:14517288,
FT ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:8846784"
FT MUTAGEN 353
FT /note="K->R: Induces decreased sumoylation and increase in
FT protein kinase activity."
FT /evidence="ECO:0000269|PubMed:21131586"
FT CONFLICT 116
FT /note="H -> D (in Ref. 5; CAA53094)"
FT /evidence="ECO:0000305"
FT CONFLICT 247..248
FT /note="WS -> LV (in Ref. 5; CAA53094)"
FT /evidence="ECO:0000305"
FT HELIX 45..47
FT /evidence="ECO:0007829|PDB:1NXK"
FT STRAND 48..50
FT /evidence="ECO:0007829|PDB:1NXK"
FT HELIX 59..61
FT /evidence="ECO:0007829|PDB:3M2W"
FT STRAND 63..73
FT /evidence="ECO:0007829|PDB:3M2W"
FT STRAND 76..83
FT /evidence="ECO:0007829|PDB:3M2W"
FT TURN 84..86
FT /evidence="ECO:0007829|PDB:3M2W"
FT STRAND 89..96
FT /evidence="ECO:0007829|PDB:3M2W"
FT HELIX 99..111
FT /evidence="ECO:0007829|PDB:3M2W"
FT STRAND 114..117
FT /evidence="ECO:0007829|PDB:3FYK"
FT STRAND 120..128
FT /evidence="ECO:0007829|PDB:3M2W"
FT STRAND 131..138
FT /evidence="ECO:0007829|PDB:3M2W"
FT STRAND 143..145
FT /evidence="ECO:0007829|PDB:1NXK"
FT HELIX 146..152
FT /evidence="ECO:0007829|PDB:3M2W"
FT HELIX 154..156
FT /evidence="ECO:0007829|PDB:6T8X"
FT HELIX 160..179
FT /evidence="ECO:0007829|PDB:3M2W"
FT HELIX 189..191
FT /evidence="ECO:0007829|PDB:3M2W"
FT STRAND 192..198
FT /evidence="ECO:0007829|PDB:3M2W"
FT STRAND 203..205
FT /evidence="ECO:0007829|PDB:3M2W"
FT STRAND 212..214
FT /evidence="ECO:0007829|PDB:3WI6"
FT HELIX 227..229
FT /evidence="ECO:0007829|PDB:6T8X"
FT HELIX 232..234
FT /evidence="ECO:0007829|PDB:1NXK"
FT HELIX 239..242
FT /evidence="ECO:0007829|PDB:3M2W"
FT HELIX 243..258
FT /evidence="ECO:0007829|PDB:3M2W"
FT STRAND 264..266
FT /evidence="ECO:0007829|PDB:4TYH"
FT STRAND 267..269
FT /evidence="ECO:0007829|PDB:1KWP"
FT HELIX 275..281
FT /evidence="ECO:0007829|PDB:1NXK"
FT STRAND 283..285
FT /evidence="ECO:0007829|PDB:2OZA"
FT HELIX 288..291
FT /evidence="ECO:0007829|PDB:3M2W"
FT STRAND 292..294
FT /evidence="ECO:0007829|PDB:6T8X"
FT HELIX 296..305
FT /evidence="ECO:0007829|PDB:3M2W"
FT TURN 310..312
FT /evidence="ECO:0007829|PDB:3M2W"
FT HELIX 316..320
FT /evidence="ECO:0007829|PDB:3M2W"
FT HELIX 323..326
FT /evidence="ECO:0007829|PDB:3M2W"
FT HELIX 328..330
FT /evidence="ECO:0007829|PDB:3M2W"
FT STRAND 335..337
FT /evidence="ECO:0007829|PDB:3M42"
FT HELIX 338..344
FT /evidence="ECO:0007829|PDB:3M2W"
FT HELIX 346..348
FT /evidence="ECO:0007829|PDB:3M2W"
FT HELIX 349..363
FT /evidence="ECO:0007829|PDB:3M2W"
FT TURN 375..377
FT /evidence="ECO:0007829|PDB:2OKR"
FT HELIX 381..389
FT /evidence="ECO:0007829|PDB:2OKR"
SQ SEQUENCE 400 AA; 45568 MW; E4EFFF11CCF288DC CRC64;
MLSNSQGQSP PVPFPAPAPP PQPPTPALPH PPAQPPPPPP QQFPQFHVKS GLQIKKNAII
DDYKVTSQVL GLGINGKVLQ IFNKRTQEKF ALKMLQDCPK ARREVELHWR ASQCPHIVRI
VDVYENLYAG RKCLLIVMEC LDGGELFSRI QDRGDQAFTE REASEIMKSI GEAIQYLHSI
NIAHRDVKPE NLLYTSKRPN AILKLTDFGF AKETTSHNSL TTPCYTPYYV APEVLGPEKY
DKSCDMWSLG VIMYILLCGY PPFYSNHGLA ISPGMKTRIR MGQYEFPNPE WSEVSEEVKM
LIRNLLKTEP TQRMTITEFM NHPWIMQSTK VPQTPLHTSR VLKEDKERWE DVKEEMTSAL
ATMRVDYEQI KIKKIEDASN PLLLKRRKKA RALEAAALAH
